Introduction The ability to selectively process visual inputs and generate appropriate actions is a crucial function of the primate brain, and one that is implicated in a variety of disorders, including attention deficit hyperactivity disorder (ADHD) and autism. Scientists in my section investigate the neuronal circuits involved in this visual function using a range of techniques, in both non-human primates and mice, in order to understand how these neuronal circuits operate under normal conditions and to identify how breakdowns in these mechanisms cause disorders of sensory-motor coordination. Contrary to prevailing models of visual attention, we recently discovered that the Superior Colliculus (SC) contributes to visual attention through mechanisms that are independent of the visual cortex: reversible local inactivation of the SC causes major deficits in visual attention but does not alter any of the known signatures of attention on neurons in visual cortex used to perform the task. Consequently, we recently proposed that attention is a byproduct of circuits centered on the basal ganglia that regulate how sensory and other signals are used for motor and non-motor decision-making (Krauzlis et al., 2014). We are working to test and identify how these subcortical circuits contribute to visual selection and attention, with the long-term goal of identifying the detailed neuronal circuit so that more specific therapeutic interventions can be developed. 1) Neuronal circuits for the control of attention in primates Most of our work is done using non-human primates, whose close homology with humans makes them the best animal model of human visual attention. 1a) fMRI and visual attention in primates In collaboration with David Leopold in the NIF, we are using fMRI in nonhuman primates to identify the complete network of cortical and subcortical areas involved in the allocation of attention during visual attention tasks. During the past year, Drs. Bogadhi and Bollimunta successfully combined reversible SC inactivation during visual attention task performance in the fMRI scanner. Their findings show that SC inactivation caused large deficits in task performance, but at the same time, BOLD signal in most cortical areas implicated in visual attention (e.g., visual areas V1, MT, MST, and also areas LIP and FEF) remained unchanged; these results extend our previous findings that activity in visual cortex is unaffected by SC inactivation (Zenon & Krauzlis, 2012). In contrast, several subcortical areas (pulvinar, caudate, putamen) showed significant reductions in BOLD during the SC inactivation and behavioral impairment; these results point to interactions between the SC, pulvinar and striatum as the basis for the observed deficits in attention performance. These results will be presented in a nanosymposium at the upcoming Society for Neuroscience meeting. 1b) Comparison of attention-related BOLD and single-unit modulation in FEF Because fMRI is an indirect measure, it is important to directly compare spiking activity to BOLD signal in cortical brain areas implicated in visual attention, both before and during SC inactivation. Among the candidate cortical areas, the frontal eye fields (FEF) is arguably the most important area to investigate, because of its well-established roles as possible salience maps for the control of attention, its role in representing decision variables during decision-making, and its anatomical connections with the SC. Dr. Bollimunta has now addressed this issue by doing fMRI and single-unit recordings in the FEF of two monkeys during a visual attention task. He has found that both BOLD and single-unit recordings in FEF show attention-related modulation that appears to remain intact during SC inactivation. These findings are an important cross-validation of our fMRI results, given that the relationship between BOLD and neuronal spiking is still not fully understood. These findings also suggest that the SC contributes to visual attention through circuits largely outside of the well-known fronto-parietal cortical network. This work will be presented at the upcoming Society for Neuroscience meeting. 1c) Testing how the striatum contributes to attention As a direct test of our idea that subcortical pathways through the basal ganglia are important for visual attention, Dr. Arcizet has been investigating the role of the caudate nucleus (one of the input nuclei for the basal ganglia) during our visual attention ask. The caudate nucleus is one of the subcortical structures identified in our fMRI results, as well as a structure we identified as a potential target based on neuroanatomy and physiology. By recording from caudate neurons during a visual attention task, Dr. Arcizet has found that caudate neurons do not simply report sensory or motor events, but instead establish a link between sensory signals and action selection. During the attention task, caudate neurons not only discriminate the location of the cued visual stimulus, they also show activity related to the animals action decision. These results support the idea that caudate neurons contribute to visual attention by linking sensory selectivity to particular motor actions; these results will be presented in a nanosymposium at the upcoming Society for Neuroscience meeting. 1d) Modeling how the superior colliculus contributes to visual attention Last year, Dr. Herman showed that neurons in the SC exhibit vigorous increases in activity triggered by color changes, and this activity is also predictive of the animals behavioral response. These results support the view that the SC contributes to the processing of any behaviorally relevant visual event, regardless of feature dimension. To test this idea quantitatively, we have now developed a model relating single-unit data to the behavioral effects of SC inactivation. Dr. Herman demonstrated that the model can predict behavioral responses during the attention task, based on the neuronal activity recorded in the SC. In addition, by scaling down the activity of in a simulated pool of neurons, the model is capable of reproducing the deficits in attention caused by SC inactivation. These results show that neuronal signals in the SC are sufficient to account for task performance, and that the deficits caused by SC inactivation can be accounted for by a straightforward reduction in the output from the SC. This work will be presented in a nanosymposium at the upcoming Society for Neuroscience meeting. 2) Role of subcortical neuronal circuits in visual detection and attention in mice Given current tools, mice provide opportunities to work out the details of neuronal circuits in ways that are not yet possible in nonhuman primates, and will help us identify worthwhile genetic and molecular targets in primates. 2a) Optogenetic stimulation of striatum in mice during visual tasks During the past year, we moved our mouse experiments into a larger space. This expanded capacity has made it possible to test lines of cre-expressing mice that allow us to target specific populations of neurons. Dr. Wang has trained mice to report changes in a visual stimulu by licking a central spout, and used transgenic lines of mice to optogenetically stimulate specific types of neurons in the striatum during performance of the task. Specifically, he has used Drd1a-Cre and A2a-Cre mice to target medium spiny neurons in the direct and indirect pathways in the striatum. The direct and indirect pathways are believed to play complementary roles in motor control, and Dr. Wangs results indicate that these same circuits also play complementary roles in controlling how visual signals are used to guide behavior. These results are consistent with our general hypothesis about how subcortical circuits contribute to visual atte